IDE196 Combinations for Solid Tumors
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: IDEAYA Biosciences
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.
Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.
Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.
As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.
Is the drug IDE196 a promising treatment for solid tumors?The information provided does not directly address the effectiveness of IDE196 (Darovasertib) for solid tumors. Therefore, we cannot determine if it is a promising treatment based on the given research articles.5671314
What safety data exists for IDE196 and its combinations for solid tumors?The provided research does not contain specific safety data for IDE196, Binimetinib, Mektovi, Crizotinib, Xalkori, Darovasertib, or LXS196. The studies focus on immune-related adverse events associated with PD-1/PD-L1 inhibitors like nivolumab and pembrolizumab, and combination therapies involving immune checkpoint inhibitors and bevacizumab. For specific safety data on IDE196 and its combinations, further research or clinical trial results would be needed.138910
What data supports the idea that IDE196 Combinations for Solid Tumors is an effective treatment?The available research does not provide specific data on the effectiveness of IDE196 Combinations for Solid Tumors. The studies mentioned focus on other treatments and conditions, such as Capivasertib for prostate cancer and mirvetuximab soravtansine for ovarian cancer, without mentioning IDE196. Therefore, there is no direct evidence from the provided information to support the effectiveness of IDE196 Combinations for Solid Tumors.2451112
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on prohibited medications that cannot be discontinued before the study. Additionally, if you join the PK substudy with pravastatin, you must refrain from taking statins or certain other drugs for at least 7 days before enrollment.
Eligibility Criteria
This trial is for adults with certain solid tumors, including metastatic uveal melanoma, skin cancer, and colorectal cancer that have specific genetic mutations or fusions. Participants must have had prior treatment with a MEK inhibitor (except for Binimetinib Combination), measurable disease, good performance status (ECOG ≤1), life expectancy over 3 months, adequate organ function and cardiac function (for Binimetinib Combination), and agree to use contraception. Exclusions include symptomatic brain metastases, pregnancy/breastfeeding women, recent thromboembolic events or surgeries.Inclusion Criteria
I am 18 years old or older.
I have a history of fainting.
I have spinal cord compression.
I have melanoma or another solid tumor with a specific mutation and it has worsened after treatment.
My heart pumps well, with an ejection fraction of 50% or higher.
I can perform daily activities with minimal help and am expected to live more than 3 months.
I have had pneumonitis or lung disease affecting the tissue and space around the air sacs.
I finished any previous cancer treatments or major surgeries at least 4 weeks ago.
I have been treated with a MEK inhibitor before.
I have a history of lung scarring or fibrosis.
Exclusion Criteria
I have previously been treated with a MEK inhibitor.
I have a muscle disorder that increases my CPK levels.
I have a history of fainting.
I am not on any medications that can't be stopped for the study.
I have had surgery to remove my stomach or part of my upper bowel, or I have another significant digestive system condition.
My tumor is MSI-H/dMMR and I haven't had immune checkpoint inhibitors.
I do not have AIDS, hepatitis B, or hepatitis C.
I have brain metastases that are causing symptoms.
I have been treated with a PKC inhibitor before.
I still have side effects from previous cancer treatments.
I am not allergic to mammalian meat products or gelatin.
My high blood pressure is not controlled by medication.
I have a history of fainting.
I have spinal cord compression.
I have no history or current signs of retinal vein occlusion.
I am not allergic to binimetinib or its components.
I have received treatments targeting ALK, MET, or ROS1.
I have a history of lung scarring or fibrosis.
I have had pneumonitis or lung disease.
My heart does not function properly.
I am not pregnant or breastfeeding.
I am currently being treated for an infection.
Treatment Details
The study tests the safety and effectiveness of IDE196 alone or in combination with Crizotinib or Binimetinib in patients whose tumors have GNAQ/11 mutations or PRKC fusions. It includes dose escalation to find the right amount of drug and then expands to more patients at this dose. The effects of food on IDE196's absorption are also studied.
9Treatment groups
Experimental Treatment
Group I: PK Substudy with Pravastatin (OBTP1B1 Substrate)Experimental Treatment1 Intervention
A PK substudy with approximately 18 patients will be nested within the IDE196 and crizotinib combination expansion cohort to evaluate the impact on the pravastatin PK profile by the steady state exposures of IDE196.
Group II: Dose Optimization Crizotinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Group III: Dose Expansion MonotherapyExperimental Treatment1 Intervention
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
Group IV: Dose Expansion Crizotinib CombinationExperimental Treatment2 Interventions
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Previously treated MUM, Treatment naïve MUM, MUM patients with human leukocyte antigen (HLA)-A\*02:01 positive status
Group V: Dose Expansion Binimetinib CombinationExperimental Treatment2 Interventions
RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
Group VI: Dose Escalation MonotherapyExperimental Treatment1 Intervention
IDE196 dosed orally, twice daily (BID) for each 28-day cycle
Group VII: Dose Escalation Crizotinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Group VIII: Dose Escalation Binimetinib CombinationExperimental Treatment2 Interventions
IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle
Group IX: Crizotinib Monotherapy with Crossover to CombinationExperimental Treatment2 Interventions
Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Cincinnati Cancer CenterCincinnati, OH
The Sarah Cannon Research Institute/Tennessee OncologyNashville, TN
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, PA
Princess Margaret Cancer CentreToronto, Canada
More Trial Locations
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Who is running the clinical trial?
IDEAYA BiosciencesLead Sponsor
References
Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis. [2022]Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73-32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85-7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%. Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.
Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer. [2019]To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients.
Association between immune-related adverse events and prognosis in patients with metastatic renal cell carcinoma treated with nivolumab. [2020]Immune-related adverse events (irAEs) develop in a subset of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The relationship between presence of irAEs and prognosis in these patients remains unknown. Thus, we evaluated the prognostic impact of irAEs caused by nivolumab therapy in mRCC patients who had received prior molecular-targeted therapies.
Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. [2021]To date, single-agent programmed cell death 1 protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint blockade has shown limited activity in recurrent epithelial ovarian cancer. Combination strategies of PD-1/PD-L1 inhibition with antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a potential therapeutic opportunity in this disease.
Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). [2022]Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel.
A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515). [2022]Prexasertib (LY2606368) is a novel, second-generation, selective dual inhibitor of checkpoint kinase proteins 1 (CHK1) and 2 (CHK2). We conducted a phase 1 trial of prexasertib to estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), to define and describe the toxicities, and to characterize the pharmacokinetics (PK) of prexasertib in pediatric patients with recurrent or refractory solid and central nervous system (CNS) tumors.
Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models. [2022]CRM1 inhibitors have demonstrated antitumor effects in ovarian and other cancers; however, rational combinations are largely unexplored. We performed a high-throughput drug library screen to identify drugs that might combine well with selinexor in ovarian cancer. Next, we tested the combination of selinexor with the top hit from the drug screen in vitro and in vivo Finally, we assessed for mechanisms underlying the identified synergy using reverse phase protein arrays (RPPA). The drug library screen assessing 688 drugs identified olaparib (a PARP inhibitor) as the most synergistic combination with selinexor. Synergy was further demonstrated by MTT assays. In the A2780luc ip1 mouse model, the combination of selinexor and olaparib yielded significantly lower tumor weight and fewer tumor nodules compared with the control group (P < 0.04 and P < 0.03). In the OVCAR5 mouse model, the combination yielded significantly fewer nodules (P = 0.006) and markedly lower tumor weight compared with the control group (P = 0.059). RPPA analysis indicated decreased expression of DNA damage repair proteins and increased expression of tumor suppressor proteins in the combination treatment group. Collectively, our preclinical findings indicate that combination with selinexor to expand the utility and efficacy of PARP inhibitors in ovarian cancer warrants further exploration.
Prognostic Impact of Immune-related Adverse Events in Gastric Cancer Patients Treated With Nivolumab. [2022]To evaluate the impact of development of nivolumab monotherapy-induced immune-related adverse events (irAEs) and continuing nivolumab with irAEs on the survival of patients with gastric cancer (GC).
Treatment of patients with cancer using PD‑1/PD‑L1 antibodies: Adverse effects and management strategies (Review). [2022]In 2020, there were an estimated 19.3 million new cancer cases and close to 10 million cancer deaths worldwide. Cancer remains one of the leading causes of death. In recent years, with the continuous improvement of our understanding of tumor immunotherapy, immunotherapeutics, such as immune checkpoint inhibitors, have gradually become a hot spot for tumor treatment. Amongst these, programmed cell death protein 1/programmed cell death protein ligand 1 (PD‑1/PD‑L1) related inhibitors, such as nivolumab and pembrolizumab, atezolizumab, avelumab and durvalumab have been shown to exhibit a high level of efficacy in several types of tumors. It has been confirmed that these inhibitors play an important role in the anti‑tumor process, significantly improving the survival rate of patients and delaying the progress of the underlying cancer. However, its method of therapeutic interference and potential for damaging the immune system has caused concern regarding its suitability. As these adverse effects are caused by an immune response to endogenous tissues, they are designated as immune‑related adverse events (irAEs). In this review, the typical irAEs reported in recent years and the management strategies adopted are highlighted, to serve as a reference in assessing the clinical response to these adverse reactions.
Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis. [2023]Immune checkpoint inhibitors (ICIs) combined with the anti-angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large-scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan-cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan-cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14-12.10, P
Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. [2023]Evaluate the antitumor activity and safety profile of the combination of mirvetuximab soravtansine and bevacizumab in patients with platinum-resistant ovarian cancer.
The efficacy and safety of Capivasertib (AZD5363) in the treatment of patients with solid tumor: a systematic review and meta-analysis of randomized clinical trials. [2023]To evaluate the clinical efficacy and safety of Capivasertib on patients with solid tumors.
SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. [2023]Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be a negative prognostic indicator in diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGN-B6A as an antibody-drug conjugate (ADC) directed to integrin beta-6 to deliver the clinically validated payload monomethyl auristatin E (MMAE) to cancer cells. The antibody component of SGN-B6A is specific for integrin beta-6 and does not bind other alpha-v family members. In preclinical studies, this ADC has demonstrated activity in vivo in models derived from non-small cell lung, pancreatic, pharyngeal, and bladder carcinomas spanning a range of antigen expression levels. In nonclinical toxicology studies in cynomolgus monkeys, doses of up to 5 mg/kg weekly for four doses or 6 mg/kg every 3 weeks for two doses were tolerated. Hematologic toxicities typical of MMAE ADCs were dose limiting, and no significant target-mediated toxicity was observed. A phase I first-in-human study is in progress to evaluate the safety and antitumor activity of SGN-B6A in a variety of solid tumors known to express integrin beta-6 (NCT04389632).
Phase I/II study of the WEE1 inhibitor adavosertib (AZD1775) in combination with carboplatin in children with advanced malignancies: Arm C of the AcSé-ESMART trial. [2023]AcSé-ESMART Arm C aimed to define the recommended dose and activity of the WEE1 inhibitor adavosertib in combination with carboplatin in children and young adults with molecularly enriched recurrent/refractory malignancies.